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121.
PURPOSE: To evaluate selective effects of ultraviolet (UV) irradiation on spontaneous and induced apoptosis in freshly extracted mice thymocytes. MATERIALS AND METHODS: Cells were exposed to UV radiation with emission peaks of 365 nm (UVA) exposures of 1620-10200 J m(-2), of 312 nm (UVB) exposures of 34-1620 J m(-2) or of 254 nm (UVC) exposures of 1.5-1620 J m(-2), and incubated for 5.5 h with or without hydrocortisone, phorbol-12-myristate-13-acetate or anti-Fas antibody. Additionally, cells were irradiated with gamma-rays (5 Gy) before UVB exposure (408 J m(-2)) at different times. Apoptosis was quantified by DNA fragmentation. RESULTS: Up to an irradiation of 5000 J m(-2), UVA exposure did not show any effect on thymocyte apoptosis, while at 10200 J m(-2) irradiation, considerable DNA fragmentation was observed. In contrast, UVB and UVC irradiation clearly inhibited natural and cortisone-induced apoptosis. Moreover, UVB inhibited apoptosis triggered by phorbol-12-myristate-13-acetate and gamma-irradiation, but not by anti-Fas antibody. CONCLUSIONS: The response of mouse thymocytes in culture to UV irradiation strongly depends on the wavelength used. It is suggested that either a survival or an apoptotic pathway occurs depending on the physiological state of the cell, spectral composition of the UV light and cell type. The possible involvement of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase in the apoptotic pathway is discussed.  相似文献   
122.
123.
Carbon isotopes (*C) have been extensively used in man to describe oxidative vs nonoxidative disposal of an exogenous load of labeled carbohydrate (*C-CHO) at rest in various experimental situations. It is hypothesized that V*CO(2) reflects *C-CHO oxidation. However, when glycogen is synthesized through the indirect pathway (which is responsible for approximately 50% of glycogen storage), *C could be lost, diluted, and exchanged in the pyruvate-lactate pool, in the pool of tricarboxylic acid cycle intermediates, as well as at the entrance of the tricarboxylic acid cycle, and along the pathway of gluconeogenesis. This could result in a lower *C/C in the glycogen stored than in the CHO administered, in an increased production of *CO(2), and, respectively, in an overestimation and an underestimation of the oxidative and nonoxidative disposal of the CHO load. Results from the present experiment offer a support to this hypothesis. Over a 10-hour period after ingestion of a (13)C-pasta meal (313+/-10 g dry mass or 258+/-8 g of glucose) in 12 healthy subjects (6 men and 6 women), exogenous CHO oxidation computed from V(13)CO(2) (recovery factor, 0.54) significantly exceeded total CHO oxidation computed by indirect respiratory calorimetry corrected for urea excretion: 154.2+/-2.6 vs 133.5+/-3.2 g. In an additional study conducted in rats, (13)C/(12)C in glycogen stores was significantly approximately 50% lower than in the (13)C-CHO ingested, over a wide range of enrichment. These results suggest that because of dilution, loss, and exchange of *C in the indirect pathway of glycogen synthesis, the oxidative vs nonoxidative disposal of exogenous *C-CHO cannot be accurately tracked from V*CO(2).  相似文献   
124.
BACKGROUND: Net whole-body and hepatic de novo lipogenesis could be more active in women than in men, but no comparison has been made between men and women in the two phases of the ovarian cycle after ingestion of a large carbohydrate meal. OBJECTIVE: We hypothesized that net whole-body de novo lipogenesis could be larger in women than men, and that glycogen and fat balance could be, respectively, lower and higher, following a large pasta meal ingested after rest or exercise. DESIGN: The metabolic response to a pasta meal (5 g dry weight/kg body mass) was studied in six men and six women (matched for age and BMI) in the follicular and luteal phases, following rest or exercise (90 min at 50% VO(2max)). Protein, glucose, and fat oxidation, and net whole-body de novo lipogenesis were computed for 10 h following ingestion of the meal using indirect respiratory calorimetry corrected for urea excretion. RESULTS: No net whole-body de novo lipogenesis was observed in any group in any situation (postrest and postexercise). When the meal was ingested following exercise, fat oxidation was significantly higher and glucose oxidation was significantly lower (P<0.05) than following the period of rest, and in a given experimental situation, the respective contributions of protein, fat, and glucose oxidation to the energy yield were similar in men and women in both phases of the cycle. CONCLUSIONS: The contribution of substrate oxidation to the energy expenditure as well as fat and glycogen balance, and the effect of a previous exercise period, were similar in men and women in both phases of the cycle following ingestion of the large carbohydrate meal.  相似文献   
125.
The neurotic personality creates numerous problems of behaviour in the infant and youth population. Given that this profile is not described in the manuals of psychopathology, we offer our criteria for its detection and treatment. One is dealing with patients who live anchored in an infantile egocentricity, intolerant in face of frustrations and highly dissatisfied. These basic symptoms are complemented by some that we describe in our questionnaire: Q-2-O ("QUESTIONARI 2, d'Osona") which might help in evaluating their intensity: anxiety, psychomotor restlessness, dysthymia, indiscipline, aggressiveness and laziness. This maturational stagnation is accompanied by the certitude that they cannot change, because "that's how they are". With a highly vigilant super-ego, they can achieve a perfect socio-school adaptation, while at home their tyranny makes them unbearable. We suggest a genetic based aetiology, but there is much in this disorder that is learned. That is where we focus its treatment. It is necessary to correct this behaviour before adult life is reached.  相似文献   
126.
'Protein Displays of the Human T Cell Receptor Alpha, Beta, Gamma and Delta Variable and Joining Regions', the 13th report of the 'IMGT Locus in Focus' section, comprises 8 figures: (1) 'Protein display of the human TRA V-REGIONs'; (2) 'Protein display of the human TRB V-REGIONs'; (3) 'Protein display of the human TRG V-REGIONs'; (4) 'Protein display of the human TRD V-REGIONs'; (5) 'Protein display of the human TRA J-REGIONs'; (6) 'Protein display of the human TRB J- REGIONs'; (7) 'Protein display of the human TRG J-REGIONs'; (8) 'Protein display of the human TRD J-REGIONs', and 4 tables entitled: (1) 'FR-IMGT and CDR-IMGT length of the human TRAV genes'; (2) 'FR-IMGT and CDR-IMGT length of the human TRBV genes'; (3) 'FR-IMGT and CDR-IMGT length of the human TRGV genes'; (4) 'FR-IMGT and CDR-IMGT length of the human TRDV genes'. These figures and tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http:// imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France.  相似文献   
127.
Alternative strategies are required to enhance the diagnosis of silent hepatitis C virus (HCV) infections in key populations at risk. Among them, HCV prevalence and bio‐behavioural data are scarce for HIV‐negative men who have sex with men (MSM) and men and trans‐women sex workers. We sought to describe and assess the potential benefits of a community‐based one‐step HCV screening and confirmatory strategy for these populations in Barcelona. The screening strategy based on a real‐time RT‐PCR assay for HCV‐RNA detection in dried‐blood spots (DBS) was validated and implemented in addition to an antibody point‐of‐care test in a community centre. HCV prevalence was assessed, and bio‐behavioural data were collected. The molecular assay was precise, reproducible, sensitive and specific. Four HIV‐negative MSM reported being currently infected (0.75% HCV self‐reported prevalence). Implementation of DBS testing was easy, and acceptability was >95%, but no silent HCV case was diagnosed (N = 580). High‐risk sexual practices and drug use for sex were reported frequently. HIV prevalence was 4.7% in MSM and 10% in sex workers. Self‐reported prevalence of other STIs ranged from 11.3% to 36.2%. In conclusion, HCV‐RNA testing in DBS showed a good performance, but the assessed one‐step strategy does not seem beneficial in this setting. Although no silent HCV infections were detected, the observed high‐risk behaviours and prevalence of other STIs suggest that HCV spread should be periodically monitored among these populations in Barcelona by means of behavioural surveillance, rapid antibody testing and molecular confirmation in DBS.  相似文献   
128.

Introduction

Alzheimer disease (AD) is a major neurodegenerative disorder which eventually results in total intellectual disability. The high global prevalence and the socioeconomic burden associated with the disease pose major challenges for public health in the 21st century. In this review we focus on both existing treatments and the therapies being developed, which principally target the β-amyloid protein.

Discussion

The amyloidogenic hypothesis proposes that β-amyloid plays a key role in AD. Several pharmacological approaches aim to reduce the formation of β-amyloid peptides by inhibiting the β-secretase and γ-secretase enzymes. In addition, both passive and active immunotherapies have been developed for the purpose of inhibiting β-amyloid peptide aggregation.

Conclusions

Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease. The lack of efficacy of solanezumab (a humanised monoclonal antibody that promotes β-amyloid clearance in the brain), demonstrated by 2 recent Phase III clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised.  相似文献   
129.
New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-PubMed, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.  相似文献   
130.
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